Human EGFR is dysregulated in many solid tumors, making it an attractive target for anticancer therapy. A number of agents that target this receptor, including antibodies, are in use or in clinical development.
Interleukin-8 (IL8) is a chemokine belonging to the CXC group of chemokines. IL8 is a survival factor for a variety of cell types, including tumor cells. Combined administration of antibodies to IL8 and EGFR has been reported to result in increased antimetastatic effects on human breast carcinoma xenografts in mice (Salcedo et al. (2002) Clin. Cancer. Res. 8:2655-2665).
Undesired side-effects of anti-EGFR treatment include adverse gastrointestinal effects, such as diarrhea, and electrolyte abnormalities, in particular hypomagnesaemia. Other adverse effects common to anti-EGFR agents include undesired dermatological side-effects, such as papulopustolar rash, usually on the face, upper back and upper torso, which generally develops in a dose-dependent manner. Findings suggest that there is a relationship between the development of rash and response and/or survival. Although most patients only see mild to moderate skin toxicity, clinical benefit of increasing the dose of the various EGFR inhibitors is expected.
Histological data indicate that rash is caused directly by EGFR inhibition in skin. Serial biopsies of skin before and after treatment revealed two main reaction patterns: a superficial dermal inflammatory cell infiltrate surrounding hyperkeratotic and ectatic follicular infundibula, and a suppurative superficial folliculitis. Follicular accumulation of neutrophilic granulocytes is considered characteristic for the skin lesion observed after EGFR inhibition. Otherwise, however, little is known about the etiology of this rash, and there are no clear evidence-based management recommendations.